Role of ammonia in tubulointerstitial injury.
Accelerated rates of ammonia production by the renal proximal tubule constitute an important adaptation to chronic renal injury. Although serving to maintain net acid excretion, this augmented production of ammonia per nephron results in increased renal cortical levels of ammonia and contributes to progressive renal injury. Ammonia fosters progressive injury via its ability to modify the third component of complement and initiate alternative complement pathway activity. This interaction of ammonia with complement incites inflammation in models of nonimmune chronic renal disease in the rat and may contribute to tissue injury in pyelonephritis involving urease-positive organisms. The long recognized in vivo association between increased renal ammoniagenesis, renal growth, and progressive injury in several models of renal disease has been advanced by the recent demonstration of ammonia as a direct stimulus to growth of renal tubular epithelium in culture. Additionally, evidence from studies of acute ischemic renal injury suggests a contributory role for ammonia in mediating tissue injury in this model. Elevated renal levels of ammonia, therefore, contribute to tubulointerstitial injury primarily through the proinflammatory and growth-promoting properties of ammonia.
Clark
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Department of Medicine, University of Minnesota, Minneapolis.
Nath
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Hostetter
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Hostetter
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D000208:Acute Disease; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002908:Chronic Disease; D006801:Humans; D009395:Nephritis, Interstitial / Q000150:complications / Q000378:metabolism*
D000641:Ammonia